Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies

Lee JH, Budanov AV, Park EJ, Birse R, Kim TE, Perkins GA, Ocorr K, Ellisman MH, Bodmer R, Bier E, Karin M · 2010 · Science · Atlas ID LEE2010

What this study shows

An early study linking Sestrin, later identified as a leucine sensor in mammals, to age-associated pathology in flies (fat accumulation, mitochondrial dysfunction, muscle and cardiac decline), prevented by TOR inhibition or AMPK activation. Sestrin sits in a negative feedback loop: TOR activity drives Sestrin expression, and Sestrin inhibits TOR back.

Abstract

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Sestrins are conserved proteins that accumulate in cells exposed to stress, potentiate adenosine monophosphate-activated protein kinase (AMPK), and inhibit activation of target of rapamycin (TOR). We show that the abundance of Drosophila sestrin (dSesn) is increased upon chronic TOR activation through accumulation of reactive oxygen species that cause activation of c-Jun amino-terminal kinase and transcription factor Forkhead box O (FoxO).

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Drosophila melanogaster (dSesn loss-of-function)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Drosophila melanogaster (dSesn loss-of-function)
Journal	Science
Year	2010
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1126/science.1182228 · PMID 20203043

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	dSesn loss of function; rapamycin; AMPK activation
Target	Sestrin -> AMPK/TOR feedback loop
Model	Drosophila
Effect	Sestrin loss causes age-related muscle, cardiac and metabolic pathology in flies; rescued by TOR inhibition or AMPK activation

In the Atlas

Links in the pathway map

Supports Sestrin2 inhibits Age-related pathology

Open questions that cite this study

Cited as supporting evidence for the open question Sensor-selective geroprotection without the metabolic penalty.

Cite this paper

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Lee, J. H., Budanov, A. V., Park, E. J., Birse, R., Kim, T. E., Perkins, G. A., Ocorr, K., Ellisman, M. H., Bodmer, R., Bier, E., & Karin, M. (2010). Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science. https://doi.org/10.1126/science.1182228

@article{LEE2010,
  author       = {Lee, J. H. and Budanov, A. V. and Park, E. J. and Birse, R. and Kim, T. E. and Perkins, G. A. and Ocorr, K. and Ellisman, M. H. and Bodmer, R. and Bier, E. and Karin, M.},
  title        = {{Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies}},
  journal      = {Science},
  year         = {2010},
  doi          = {10.1126/science.1182228},
  note         = {PMID: 20203043},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record LEE2010) [Data set]. https://mtor-atlas.org/study/LEE2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LEE2010,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LEE2010},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LEE2010/},
  doi          = {10.5281/zenodo.22059963}
}

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